TABLE 1.
Calculation of clinically relevant concentrations of drug for in vitro resistance selection studies
| Parametera | DOR | RPV | EFV |
|---|---|---|---|
| Clinical dose (mg) | 100 | 25 | 600 |
| C24 (nM) | 610b | 260 | 5,600 |
| IC50 in 100% NHS (nM) | 12.3 | 56 | 30 |
| IQ | 49.6 | 4.6 | 187 |
| IC50 in 10% NHS (nM) | 3.7 | 4.5 | 2.6 |
| Concn calculated for resistance selection in 10% NHS (nM) (IQ × IC50 in 100% NHS) | 184 | 21 | 486 |
| Selected concn for resistance selection in 10% NHS (nM) | 200 | 20 | 500 |
a
C24, clinical trough concentration. IQ was calculated as the ratio of C24/IC50 in 100% NHS.
b
The trough concentration of DOR used in this calculation was based on the preliminary phase 1a trial. However, the trough concentration was projected to be 830 nM, based on both phase 1 and 2 trials, which was used to calculate the IQs described above.